PROJECT ABSTRACT This supplement proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) research to be carried out at the NYU VTEU. We will participate in the implementation of a COVID-19 vaccine efficacy trial ?A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, A Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19.? In addition to the above, and as a supplement request to further address the mission of the CoVPN, we are requesting funds for other CoVPN studies ?and other COVID-related research?. We plan to conduct an additional study within the CoVPN ? Monoclonal Antibody (mAb) Studies: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS- CoV-2 Monoclonal Antibodies in Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected with SARS-CoV-2. With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. The vaccine trial we will conduct is a phase 3, placebo-controlled, double- blinded study will test the efficacy of AZD1222, a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein, to modify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from up to 100 clinical trial sites across the US, using data analytics to target high risk individuals with a diverse racial and ethnic profile. The MAB study we will conduct is a pivotal phase 3 randomized, double-blind, placebo-controlled study in adults with household contact exposure to individuals with SARS-CoV-2 infection in geographic areas with an active COVID-19 outbreak. An ideal agent for prophylaxis should be fast acting and highly effective and should protect against multiple viral variants. A monoclonal antibody (mAb) combination therapy, with two different monoclonal antibodies that bind distinct regions of the portion of the SARS-CoV-2 spike (S) protein that bind to and facilitate entry into host cells, has been developed in order to achieve these goals. A mAb combination against SARS-CoV-2 for post-exposure prophylaxis that can either prevent the development of disease or reduce viral acquisition or shedding could be key to reducing transmission of the virus and limiting symptoms and adverse outcomes following infection. We also request site preparedness funds, and fund for Dr Mulligan?s role as national PI of an additional MAB study (Lilly MAB in nursing home residents and staff, for COVID-19 prevention).